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UniQure and Apic Bio Enter Global Licensing Agreement for ALS Gene Therapy Caused by Mutations in SOD1

January 31, 2023

Rare Daily Staff

UniQure and Apic Bio have entered into a global licensing agreement for the experimental gene therapy APB-102 to treat SOD1 amyotrophic lateral sclerosis, a rare, genetic form of the disease.

Under the agreement, UniQure acquires global rights for the development and commercialization of APB-102, adding to its pipeline of gene therapies to treat neurological disorders. The U.S. Food and Drug Administration has cleared the investigational new drug (IND) application for APB-102 and has granted Orphan Drug and Fast Track designations.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons, leading to muscle weakness and eventual paralysis. Most patients face mortality within five years of disease onset due to respiratory failure. ALS can be caused by multiple genetic mutations and can be sporadic (spontaneous mutations) or familial (inherited mutations). Familial mutations account for approximately ten percent of ALS cases, and of these, approximately twenty percent are linked to a mutation in the SOD1 gene that codes for the enzyme superoxide dismutase 11. SOD1-linked ALS is most likely caused by toxic mutant forms of the superoxide dismutase 1 (SOD1) protein (a gain-of-function mutation). Current approved ALS treatments only delay disease progression without addressing the underlying genetic causes of the disease.

APB-102 is designed to be a novel, one-time, intrathecally administered gene therapy for ALS caused by mutations in SOD1, a rapidly progressing, rare motor neuron disease that leads to loss of everyday functions and is uniformly fatal. Mutations in the SOD1 gene of ALS account for approximately one-fifth of all inherited forms of this fatal disease. APB-102 is comprised of a recombinant AAVrh10 vector that expresses a micro ribonucleic acid (miRNA) designed to knock down the expression of SOD1 with the goal of slowing down or potentially reversing the progression of ALS in patients with SOD1 mutations.

“The licensing of APB-102 provides UniQure with another clinical stage program that is strategically aligned with our current pipeline and highly complementary with our AMT-161 program for the treatment of ALS caused by mutations in the c9orf72 gene,” said Ricardo Dolmetsch, president of research and development at UniQure. “Together, these ALS gene therapy candidates have the potential to address most familial forms of ALS and transform the lives of thousands of patients around the world suffering from this devastating disease.”

The clinical development of APB-102 is based on nearly 30 years of research demonstrating the link between the SOD1 gene mutation and ALS. Preclinical studies in a SOD1-ALS mouse model demonstrated that APB-102 greatly enhanced survival in affected mice. Relevant SOD1 reduction in spinal cord motor neurons also was demonstrated in rodents, as well as in non-human primates at proposed clinical doses.

Under the terms of the agreement, UniQure will make an initial cash payment of $10 million. In addition, UniQure will pay Apic Bio up to $45 million in milestones upon achievement of regulatory approvals in the U.S. and Europe and pre-specified annual net sales, and a tiered royalty on net sales ranging from the mid-single digits to low double digits.

UniQure expects to initiate a phase 1/2 clinical study of APB-102 in the second half of 2023.

Photo: Ricardo Dolmetsch, president of research and development at UniQure

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